Alpha lipoic acid (α-LA) is a potent biological antioxidant that is found naturally in the human body at very low concentrations, primarily in the mitochondria. However, synthetic α-LA is commercially available as a nutritional supplement and has been shown to be effective at ameliorating symptoms in diseases with an underlying oxidative stress component. High blood cholesterol is a major cardiovascular disease (CVD) risk factor and is responsive to diet and lifestyle modifications. In addition to high blood cholesterol, there is increasing evidence that supports the independent role of oxidized lipids and lipoproteins, chiefly oxidized low-density lipoproteins (Ox-LDL), in the development of CVD. Lowering total blood cholesterol (TC), LDL cholesterol (LDL-C), and triglycerides (TG) and raising high-density lipoprotein cholesterol (HDL-C) levels is the most desirable metabolic state for maximum protection against CVD, but can be difficult to achieve through diet and exercise alone. With emerging evidence of reduced LDL-C and TG, increased HDL-C, and blunting of oxidative susceptibility of lipoproteins by α-LA, its use alone or in combination with other dietary supplements may be an effective strategy to modulate multiple metabolic targets of oxidative stress and cholesterol metabolism to reduce CVD risk. This review examines the current evidence for the use of α-LA in CVD risk reduction and identifies the remaining gaps that must be addressed in this area of research.